Summary: Though opioids and NSAIDs are the most common painkillers used in those with chronic pain, they have their downsides. NSAIDs are only good for mild to moderate pain, and opioids cause dependence. However, many other painkillers are known to science, but many are not prescribed as they cause significant sedation and one might need to look for opioid addiction treatment alongside. However, researchers can now test millions of molecules using new methods like computer simulations. They have now identified six new molecules that may be the non-opioid treatment for chronic pain.
There are many painkillers. However, the most commonly used painkillers are non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Among these two categories of drugs, opioids are better for moderate to severe pain. However, opioids are prone to addiction and one might need to get opioid addiction treatment in the longer run.. Thus, researchers are looking for safer painkillers that do not cause addiction or sedation and yet help suppress pain when used alone or in combination with opioids.
To find non addictive pain medicine, researchers are exploring other drug categories. For example, they know drugs like clonidine and dexmedetomidine, which are both good at pain suppression. However, these drugs are rarely used outside the hospitals as they cause significant sedation. Nonetheless, in many early studies, researchers have shown that separating sedative effects from analgesic effects is possible. Furthermore, early studies show that these effects occur due to the impact of existing drugs like clonidine on too many different brain pathways. Thus, there is a need to find more selective molecules that suppress pain pathways without causing sedation.
Six Molecules Out Of 300 Million Identified As Candidate Drugs
In recent years, a lot has changed in pharmaceutical or medical research. A few decades back, testing 300 million molecules would have been an impossible task. However, now it is possible, thanks to improvements in computational sciences. Suboxone treatment is one such advancement. To identify the new molecules that could help suppress pain and yet not cause sedation, researchers used a data bank of 300 molecules. Researchers also know the structure of receptors that these chemicals must block.
As one can understand that it is a massive task. It is like testing 300 million keys to open a lock and find a few viable keys from them. Doing it manually will take decades, if not more. It is like looking for a needle in a haystack. However, using computer simulation, it can be done much faster. Researchers feed the chemical structure of 300 million molecules to the computer and try to find which of them would fit on the specific receptors.
This new research project was a part of a five-year grant from the Defense Advanced Research Projects Agency (DARPA). The aim of the project was to find alternatives to opioids, non-opioid treatment for chronic pain, drugs that can be used alone or in conjunction with opioids for pain suppression1. In the study, researchers found 48 molecules that could bind to specific receptors in the brain and help relieve the pain. They further tested these molecules in the mice model, and six appeared to work. Moreover, these six molecules can alleviate pain without causing addiction or sedation.
Of course, these are still early days, and molecules have only been tested in animal models and computer simulations. There is still a need to test these molecules in humans and understand if they are safe for use. Nonetheless, researchers say their study provides hope to more than 50 million Americans with chronic pain. Most of these people are living with several comorbidities and require painkillers safe for prolonged use. In the future, researchers plan to test these molecules in clinical trials, using them alone or in combination with opioids. Even if they help better with opioids, this will help lower the dose of opiates.
By Gurpreet Singh Padda, MD, MBA, MHP